Data from this study indeed reveal that CDT can overcome radio-resistance of PCa cells by intervening the repair of the radiation-induced DNA double-strand break (DSB) and ataxia telangiectasia mutated (ATM)-dependent DNA damage checkpoint responses. Thus, we decided to explore the effect of CDT on radio-resistant PCa cells. Several studies have shown some promising therapeutic effect of CDT, derived from other bacterial species, on oral cancer cells. In addition, the nuclear-translocated CdtB exhibits type I deoxyribonuclease activity, which causes DNA damage leading to cell-cycle arrest at G2/M. Cellular cholesterol plays an important role in mediating CDT binding to the cell membrane, where it serves as a portal for CdtB delivery into host cells and induction of cell intoxication. In a holotoxin containing all the three subunits, CdtA and CdtC are to interact with the cell membrane and enable the translocation of CdtB across the cell membrane. It is a tripartite protein toxin composed of the 3 subunits, CdtA, CdtB, and CdtC, that are encoded by an operon comprising cdtA, cdtB, and cdtC. Therefore, it is imperative to develop a strategy to overcome radio-resistant phenotype of these cells in order to maximize the efficacy of radiation therapy.Ĭytolethal distending toxin (CDT) is a bacterial genotoxin. Reduced expression of DAB2IP in PCa cells also induces epithelial-mesenchymal transition (EMT), leading to cancer metastasis, and these cells acquire radio-resistance to ionizing radiation (IR)-induced apoptosis. Loss of DAB2IP expression in PCa cells has been reported to provide a survival advantage and resistance to stress-induced apoptosis. ĭOC-2/DAB2 interactive protein (DAB2IP) is a potent tumor suppressor in PCa, modulating several pathways including that of mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B (Akt). Although recent advances in radiotherapy have improved the disease-free survival rates of patients with disseminated PCa, disease recurrence remains inevitable. However, some of these patients present with intrinsic radio-resistance or develop radio-resistance prior to or after radiotherapy. For patients with inoperable disease or high risk of cancer recurrence, radiation therapy is considered an optimal choice. Prostate cancer (PCa) is one of the most prevalent male cancers in many western developed countries, and its incidence is increasing worldwide.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |